1-phenyl imidazol-2-one biphenylmethyl compounds for treatment of circulatory disorders

ABSTRACT

A class of 1-phenyl imidazol-2-one biphenylmethyl compounds is described for use in treatment of circulatory disorders. Compounds of particular interest are angiotensin II antagonists of the formula  
                 
 
     wherein each of R 1 , R 2  and R 3  is independently selected from hydrido, alkyl, alkoxy, cyano, halo, hydroxy, carboxyl, alkoxycarbonyl, formyl and acetyl; alkylcarbonyl and haloalkylcarbonyl; with the proviso that at least one of R 1 , R 2  and R 3  must be a substituent other than hydrido, and with the further proviso that when each of R 1  and R 3  is hydrido, then R 2  cannot be chloro; wherein R 4  is hydrido; wherein R 5  is alkyl; and wherein R 6  is tetrazolyl; or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof. These compounds are particularly useful in treatment or control of hypertension and congestive heart failure.

FIELD OF THE INVENTION

[0001] Non-peptidic 1-phenyl imidazol-2-one biphenylmethyl compounds aredescribed for use in treatment of circulatory disorders such ashypertension and congestive heart failure. Of particular interest areangiotensin II antagonist compounds provided by imidazol-2-one compoundshaving a mono- or poly-substituted phenyl moiety attached to a nitrogenatom of the imidazole-2-one nucleus and having a biphenylmethyl moietyattached to other nitrogen atom of the imidazol-2-one nucleus.

BACKGROUND OF THE INVENTION

[0002] The renin-angiotensin system is one of the hormonal mechanismsinvolved in regulation of pressure/volume homeostasis and in expressionof hypertension. Activation of the renin-angiotensin cascade begins withrenin secretion from the juxtaglomerular apparatus of the kidney andculminates in the formation of angiotensin II, the primary activespecies of this system. This octapeptide, angiotensin II, is a potentvasoconstrictor agent and also produces other physiological effects suchas promoting aldosterone secretion, promoting sodium and fluidretention, inhibiting renin secretion, increasing sympathetic nervoussystem activity, increasing vasopressin secretion, causing positivecardiac inotropic effect and modulating other hormonal systems.

[0003] Previous studies have shown that antagonizing angiotensin II atits receptors is a viable approach to inhibit the renin-angiotensinsystem, given the pivotal role of this octapeptide which mediates theactions of the renin-angiotensin system through interaction with varioustissue receptors. There are several known angiotensin II antagonists,most of which are peptidic in nature. Such peptidic compounds are oflimited use due to their lack of oral bioavailability or their shortduration of action. Also, commercially-available peptidic angiotensin IIantagonists (e.g., Saralasin) have a significant residual agonistactivity which further limit their therapeutic application.

[0004] Non-peptidic compounds with angiotensin II antagonist propertiesare known. For example, the sodium salt of2-n-butyl-4-chloro-1-(2-chlorobenzyl)imidazole-5-acetic acid hasspecific competitive angiotensin II antagonist activity as shown in aseries of binding experiments, functional assays and in vivo tests [P.C. Wong et al, J. Pharmacol. Exp. Ther., 247(1), 1-7 (1988)]. Also, thesodium salt of 2-butyl-4-chloro-1-(2-nitrobenzyl) imidazole-5-aceticacid has specific competitive angiotensin II antagonist activity asshown in a series of binding experiments, functional assays and in vivotests [A. T. Chiu et al, European J. Pharmacol., 157, 31-21 (1988)]. Afamily of 1-benzylimidazole-5-acetate derivatives has been shown to havecompetitive angiotensin II antagonist properties [A. T. Chiu et al, J.Pharmacol. Exa. Ther., 250(3), 867-874 (1989)]. U.S. Pat. No. 4,816,463to Blankey et al describes a family of4,5,6,7-tetrahydro-1H-imidazo(4,5-c)-tetrahydro-pyridine derivativesuseful as antihypertensives, some of which are reported to antagonizethe binding of labelled angiotensin II to rat adrenal receptorpreparation and thus cause a significant decrease in mean arterial bloodpressure in conscious hypertensive rats. EP No. 253,310, published Jan.20, 1988, describes a series of aralkyl imidazole compounds, includingin particular a family of biphenylmethyl substituted imidazoles, asantagonists to the angiotensin II receptor. EP No. 323,841 publishedJul. 12, 1989 describes four classes of angiotensin II antagonists,namely, biphenylmethylpyrroles, biphenylmethylpyrazoles,biphenylmethyl-1,2,3-triazoles and biphenylmethyl4-substituted-4H-1,2,4-triazoles, including the compound3,5-dibutyl-4-[(21-carboxybiphenyl-4-yl)methyl]-4H-l,2,4-triazole. U.S.Pat. No. 4,880,804 to Carini et al describes a family ofbiphenylmethylbenzimidazole compounds as angiotensin II receptorblockers for use in treatment of hypertension and congestive heartfailure.

[0005] There are several families of known compounds having one or twooxo substituents on a triazole ring. For example, East German Patent No.160,447 published Aug. 3, 1983 describes a family of1,2,4-triazolin-5-one compounds, specifically 2,4-dihydro-4,5-bis(phenylmethyl)-3H-1,2,4-triazol-3-one, for use as herbicides. BelgianPatent No. 806,146 published Oct. 16, 1972 describes a family oftriazolinone compounds, including the compound(3-(4-m-chlorophenyl-1-piperazinyl)-propyl)-3,4-diethyl-1,2,4-triazolin-5-one, having tranquilizer,hypotensive and analgesic activities. Belgian Patent No. 631,842published Feb. 28, 1963 describes a family of 1,2,4-triazolones havinghypnotic, tranquilizer, narcotic, sedative and analgetic activities,which includes a class of 4-N-aralkyl -1,2,4-triazol-5-one compounds. EP#7,180 published Jun. 15, 1978 describes a family of 1,2-disubstituted-4-alkyl-1,2,4-triazolidine-3,5-dione compounds having a wide variety ofactivities, such as antiulcer, bronchodilator, antifertility andcardiovascular-related activities which include antihypertensive,antiarrhythmic, platelet aggregation inhibition and smooth muscleactivities. EP #283,310 published Mar. 18, 1987 describes a family ofN¹-diarylmethyl-N²-aminoalkyl-diaza-heterocyclic derivatives fortreating cerebral vascular and ischemic diseases and for protectingagainst anoxia.

[0006] There are several families of known compounds having an oxo groupattached to a imidazole biphenylmethyl nucleus. For example, U.S. Pat.No. 5,177,097 to Poss describes acyl amidine and acyl guanidinebiphenylmethyl compounds as angiotensin II antagonists, includingimidazole-4-one-type biphenylmethyl compounds such as4′-[[4.5-Dihydro-5-methyl-4-oxo-2-(propylamino)-1H-imidazol-1-yl]methyl]-[1,1′-biphenyl]-2-carboxylic acid, trifluoroacetate (1:1)salt. U.S. Pat. No. 5,087,634 to Reitz et al describes a class ofN-substituted imidazole-2-one biphenylmethyl compounds as angiotensin IIantagonists, including the compound1-phenyl-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one.In PCT Application WO 91/14679 published Oct. 3, 1991, there isdescribed a family of imidazol-4-one biphenylmethyl compounds asangiotensin II antagonists, including compounds having the 5-position ofthe imidazol-4-one moiety substituted with spirocyclopentyl, or diethyl,or other alkyl groups. EP #475,898 published Mar. 18, 1992 describes aclass of imidazol-4-one and triazol-3-one biphenylmethyl compounds asangiotensin II antagonists, including the compound2-(n-Butyl)-4-ethyl-5-oxo-1-[2′-(1H-tetrazol-5-yl)biphenyl-4-ylmethyl]-4,5-dihydro-1H-imidazole. In PCT Application WO92/07834 published May 14, 1992, there is described a family ofN-substituted imidazol-2-one biphenylmethyl compounds as angiotensin IIantagonists, including the compound4-butyl-1-(2-chlorophenyl)-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-yl]methyl-2H-imidazole-2-one.

DESCRIPTION OF THE INVENTION

[0007] A class of mono- or polysubstituted 1-phenyl-imidazol -2-onebiphenylmethyl compounds useful in treating circulatory disorders,particularly cardiovascular disorders, is defined by Formula I:

[0008] wherein each of R¹, R² and R³ is independently selected fromhydrido, alkyl, alkoxy, cyano, halo, hydroxy, nitro, amino, alkylamino,carboxyl, alkoxycarbonyl, formyl, alkylcarbonyl and haloalkylcarbonyl;with the proviso that at least one of R¹, R² and R³ must be asubstituent other than hydrido, and with the further proviso that wheneach of R¹ and R³ is hydrido, then R² cannot be chloro; wherein R⁴ isselected from hydrido, alkyl, halo, haloalkyl, formyl, carboxyl andalkoxyalkyl; wherein R⁵ is selected from alkyl, phenyl, phenylalkyl,cycloalkyl and cycloalkylalkyl; and wherein R⁶ is an acidic groupselected from COOH and

[0009] or a stereoisomer or a tautomer thereof or apharmaceutically-acceptable salt thereof.

[0010] Regioisomers of compounds of Formula I are also embraced as partof the invention, particularly those regioisomers formed by varioussubstitutions on nitrogen atoms of the imidazole ring relative tosubstitutions on the carbon atoms of the imidazole ring. For purposes ofnomenclature, a numbering system for the imidazole ring is shown belowfor a preferred set of compounds of the invention within Formula I:

[0011] wherein each of R¹, R², R³, R⁴, R⁵ and R⁶ is defined above.

[0012] Compounds of Formula I would be useful in treating a variety ofcirculatory disorders and circulatory-related disorders, includingcardiovascular disorders, such as hypertension, congestive heart failureand arteriosclerosis, and to treat other disorders such as glaucoma.These compounds would also be useful as adjunctive therapies. Forexample, compounds of Formula I may be used in combination with otherdrugs, such as a diuretic, to treat hypertension. Also, compounds ofFormula I could be used in conjunction with certain surgical procedures.For example, these compounds could be used to prevent post-angioplastyre-stenosis, or to treat coronary hypertrophy arising from aortalstenosis. Compounds of Formula I are therapeutically effective intreatment of cardiovascular disorders by acting as antagonists to, orblockers of, the angiotensin II (AII) receptor. Compounds of Formula Iwould be therapeutically effective in treatment of the above-mentionedcirculatory and cardiovascular disorders or would be precursors to, orprodrugs of, therapeutically-effective compounds.

[0013] A preferred class of compounds consists of those compounds withinFormula I wherein each of R¹, R² and R³ is independently selected fromhydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, methoxy,ethoxy, propoxy, isopropoxy, tert-butoxy, cyano, fluoro, chloro, bromo,iodo, hydroxy, nitro, amino, N-methylamino, N,N-dimethylamino,N-ethylamino, N,N-diethylamino, carboxyl, methoxycarbonyl,ethoxycarbonyl, formyl, methylcarbonyl, ethylcarbonyl andtrifluoromethylcarbonyl; with the proviso that at least one of R¹, R²and R³ must be a substituent other than hydrido, and with the furtherproviso that when each of R¹ and R³ is hydrido, then R² cannot bechloro; wherein R⁴ is selected from hydrido, methyl, fluoro, chloro,monofluoromethyl, difluoromethyl, trifluoromethyl, formyl, carboxyl anddimethoxymethyl; wherein R⁵ is selected from methyl, ethyl, n-propyl,isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl,isopentyl, neopentyl, phenyl, benzyl, phenethyl, cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl,cyclopropylethyl, cyclobutylmethyl, cyclobutylethyl, cyclopentylmethyl,cyclopentylethyl, cyclohexylmethyl and cyclohexylethyl; and wherein R⁶is an acidic group selected from COOH and

[0014] or a stereoisomer or a tautomer thereof or apharmaceutically-acceptable salt thereof.

[0015] A first family of more preferred compounds consists of thosecompounds within Formula I wherein R¹ is selected from methyl, ethyl,n-propyl, isopropyl, tert-butyl, hydroxy, methoxy, fluoro, bromo, iodo,carboxyl, amino, cyano, formyl, methylcarbonyl andtrifluoromethylcarbonyl; wherein each of R², R³ and R⁴ is hydrido;wherein R⁵ is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl,sec-butyl, isobutyl, tert-butyl and n-pentyl; and wherein R⁶ is

[0016] or a stereoisomer or a tautomer thereof or apharmaceutically-acceptable salt thereof.

[0017] A group of specific compounds of particular interest within thisfirst family of more preferred compounds of Formula I consists ofmono-substituted-phenyl-type compounds, their stereoisomers andtautomers, and the pharmaceutically-acceptable salts thereof, saidcompounds consisting of

[0018] 1-(2-methylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0019] 1-(2-ethylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0020] 1-(2-propylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0021] 1-(2-isopropylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0022] 1-(2-tertbutylphenyl)-4-propyl-l,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0023] 1-(2-fluorophenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0024] 1-(2-chlorophenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0025] 1-(2-bromophenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0026] 1-(2-iodophenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0027] 1-(2-methoxyphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0028] 1-(2-hydroxyphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0029] 1-(2-cyanophenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0030] 1-(2-carboxyphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0031] 1-(2-aminophenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0032] 1-(2-acetylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-bipheny1]-4-ylmethyl]-2H-imidazol-2-one;

[0033] 1-(2-trifluoroacetylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0034] 1-(2-methylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0035] 1-(2-ethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0036] 1-(2-propylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0037] 1-(2-isopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0038] 1-(2-tertbutylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0039] 1-(2-fluorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0040] 1-(2-chlorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1l-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0041] 1-(2-bromophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0042] 1-(2-iodophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0043] 1-(2-methoxyphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0044] 1-(2-hydroxyphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0045] 1-(2-cyanophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0046] 1-(2-carboxyphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0047] 1-(2-aminophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0048] 1-(2-acetylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0049]1-(2-trifluoroacetylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0050] 1-(2-methylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0051] 1-(2-ethylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0052] 1-(2-propylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0053] 1-(2-isopropylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0054] 1-(2-tertbutylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0055] 1-(2-fluorophenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0056] 1- (2-chlorophenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0057] 1-(2-bromophenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0058] 1-(2-iodophenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0059] 1-(2-methoxyphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0060] 1-(2-hydroxyphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0061] 1-(2-cyanophenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0062] 1-(2-carboxyphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0063] 1-(2-aminophenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0064] 1-(2-acetylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one; and

[0065] 1-(2-trifluoroacetylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one.

[0066] A group of specific compounds of particular interest within thisfirst family of more preferred compounds of Formula I consists ofmono-substituted-phenyl-type compounds, their stereoisomers andtautomers, and the pharmaceutically-acceptable salts thereof, saidcompounds consisting of

[0067] 1-(2-methylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0068] 1-(2-ethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0069] 1-(2-propylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0070] 1-(2-isopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0071] 1-(2-tertbutylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0072] 1-(2-fluorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0073] 1-(2-chlorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0074] 1-(2-bromophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0075] 1-(2-iodophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0076] 1-(2-methoxyphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0077] 1-(2-hydroxyphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0078] 1-(2-cyanophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0079] 1-(2-carboxyphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0080] 1-(2-aminophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one.

[0081] 1-(2-acetylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one; and

[0082] 1-(2-trifluoroacetylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one.

[0083] A second family of more preferred compounds consists of thosecompounds within Formula I wherein each of R¹, R² and R³ isindependently selected from methyl, ethyl, n-propyl, isopropyl,tert-butyl, hydroxy, methoxy, fluoro, chloro, bromo, iodo, carboxyl,amino, cyano, formyl, methylcarbonyl and trifluoromethylcarbonyl;wherein R³ may further be hydrido; wherein R⁴ is hydrido; wherein R⁵ isselected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl,isobutyl, tert-butyl and n-pentyl; and wherein R⁶ is

[0084] or a stereoisomer or a tautomer thereof or apharmaceutically-acceptable salt thereof.

[0085] A group of specific compounds of particular interest within thissecond family of more preferred compounds of Formula I consists ofpoly-substituted-phenyl-type compounds, their stereoisomers andtautomers, and the pharmaceutically-acceptable salts thereof, saidcompounds consisting of

[0086] 1-(2,6-dimethylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0087] 1-(2-ethyl-6-methylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0088] 1-(2-propyl-6-methylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0089]1-(2-isopropyl-6-methylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0090]1-(2-tertbutyl-6-methylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0091] 1-(2-fluoro-6-methylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0092] 1-(2-chloro-6-methylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0093] 1-(2-bromo-6-methylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0094] 1-(2-methoxy-6-methylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0095] 1-(2-carboxy-6-methylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0096] 1-(2-acetyl-6-methylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0097] 1-(2,6-diethylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0098] 1-(2-propyl-6-ethylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0099] 1-(2-isopropyl-6-ethylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0100] 1-(2-tertbutyl-6-ethylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0101] 1-(2-fluoro-6-ethylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0102] 1-(2-chloro-6-ethylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0103] 1-(2-bromo-6-ethylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0104] 1-(2-methoxy-6-ethylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0105] 1-(2-carboxy-6-ethylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0106] 1-(2-acetyl-6-ethylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0107]1-(2-methyl-6-isopropylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0108] 1-(2-ethyl-6-isopropylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0109]1-(2-propyl-6-isopropylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0110] 1-(2,6-diisopropylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0111]1-(2-tertbutyl-6-isopropylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0112]1-(2-fluoro-6-isopropylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0113]1-(2-chloro-6-isopropylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0114] 1-(2-bromo-6-isopropylphenyl)-4-propyl-1,3-dihydro-?-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0115]1-(2-methoxy-6-isopropylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0116]1-(2-carboxy-6-isopropylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0117]1-(2-acetyl-6-isopropylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0118]1-(2-methyl-6-tertbutylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0119] 1-(2-ethyl-6-tertbutylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0120]1-(2-propyl-6-tertbutylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyll-2H-imidazol-2 -one;

[0121] 1-(2-isopropyl-6-tertbutylpheny)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0122] 1- (2, 6-ditertbutylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol -5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0123]1-(2-fluoro-6-tertbutylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0124]1-(2-chloro-6-tertbutylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]l-2H-imidazol-2-one;

[0125] 1-(2-bromo-6-tertbutylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0126]1-(2-methoxy-6-tertbutylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0127]1-(2-carboxy-6-tertbutylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0128] 1-(2-acetyl-6-tertbutylphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0129] 1-(2-methyl-6-fluorophenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0130] 1-(2-ethyl-6-fluorophenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0131] 1-(2-propyl-6-fluorophenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0132]1-(2-isopropyl-6-fluorophenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0133]1-(2-tertbutyl-6-fluorophenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0134] 1-(2,6-difluorophenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0135] 1-(2-chloro-6-fluorophenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0136] 1-(2-bromo-6-fluorophenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0137] 1-(2-methoxy-6-fluorophenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0138] 1-(2-carboxy-6-fluorophenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0139] 1-(2-acetyl-6-fluorophenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0140] 1-(2-methyl-6-chlorophenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0141] 1-(2-ethyl-6-chlorophenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0142] 1-(2-propyl-6-chlorophenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0143] 1-(2-isopropyl-6-chlorophenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0144]1-(2-tertbutyl-6-chlorophenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0145] 1-(2-fluoro-6-chlorophenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0146] 1-(2,6-dichlorophenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0147] 1-(2-bromo-6-chlorophenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0148] 1-(2-methoxy-6-chlorophenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0149] 1-(2-carboxy-6-chlorophenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0150] 1-(2-acetyl-6-chlorophenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0151] 1-(2-methyl-6-methoxyphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-blphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0152] 1-(2-ethyl-6-methoxyphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0153] 1-(2-propyl-6-methoxyphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0154]1-(2-isopropyl-6-methoxyphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0155]1-(2-tertbutyl-6-methoxyphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0156] 1-(2-fluoro-6-methoxyphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0157] 1-(2-chloro-6-methoxyphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0158] 1-(2-bromo-6-methoxyphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0159] 1-(2-methoxy-6-methoxyphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0160] 1-(2-carboxy-6-methoxyphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0161] 1-(2-acetyl-6-methoxyphenyl)-4-propyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0162] 1-(2,6-dimethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0163] 1-(2-ethyl-6-methylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0164] 1-(2-propyl-6-methylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmeLhyl]-2H-imidazol-2-one;

[0165] 1-(2-isopropyl-6-methylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0166] 1-(2-tertbutyl-6-methylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0167] 1-(2-fluoro-6-methylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0168] 1-(2-chloro-6-methylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0169] 1-(2-bromo-6-methylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0170] 1-(2-methoxy-6-methylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0171] 1-(2-carboxy-6-methylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0172] 1-(2-acetyl-6-methylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0173] 1-(2-methyl-6-ethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0174] 1-(2,6-diethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0175] 1-(2-propyl-6-eLhylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0176] 1-(2-isopropyl-6-ethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol2-one;

[0177] 1-(2-tertbutyl-6-ethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0178] 1-(2-fluoro-6-ethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0179] 1-(2-chloro-6-ethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0180] 1-(2-bromo-6-ethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0181] 1-(2-methoxy-6-ethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0182] 1-(2-carboxy-6-ethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0183] 1-(2-acetyl-6-ethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0184] 1-(2-methyl-6-isopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0185] 1-(2-ethyl-6-isopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0186] 1-(2-propyl-6-isopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0187] 1-(2,6-diisopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0188]1-(2-tertbutyl-6-isopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0189] 1-(2-fluoro-6-isopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0190] 1-(2-chloro-6-isopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0191] 1-(2-bromo-6-isopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0192]1-(2-methoxy-6-isopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0193]1-(2-carboxy-6-isopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0194] 1-(2-acetyl-6-isopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0195] 1-(2-methyl-6-tertbutylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0196] 1-(2-ethyl-6-tertbutylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0197] 1-(2-propyl-6-tertbutylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0198]1-(2-isopropyl-6-tertbutylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyll-2H-imidazol-2-one;

[0199] 1-(2,6-ditertbutylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0200] 1-(2-fluoro-6-tertbutylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0201] 1-(2-chloro-6-tertbutylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0202] 1-(2-bromo-6-tertbutylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0203]1-(2-methoxy-6-tertbutylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0204]1-(2-carboxy-6-tertbutylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0205] 1-(2-acetyl-6-tertbutylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0206] 1-(2-methyl-6-fluorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0207] 1-(2-ethyl-6-fluorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0208] 1-(2-propyl-6-fluorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0209] 1-(2-isopropyl-6-fluorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0210] 1-(2-tertbutyl-6-fluorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl) [1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0211] 1-(2,6-difluorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0212] 1-(2-chloro-6-fluorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0213] 1-(2-bromo-6-fluorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0214] 1-(2-methoxy-6-fluorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0215] 1-(2-carboxy-6-fluorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0216] 1-(2-acetyl-6-fluorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl) [1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2 -one;

[0217] 1- (2-methyl-6-chlorophenyl) -4-butyl-1, 3-dihydro-3- [2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0218] 1-(2-ethyl-6-chlorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0219] 1-(2-propyl-6-chlorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0220] 1-(2-isopropyl-6-chlorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmeLhyl]-2H-imidazol-2-one;

[0221] 1-(2-tertbutyl-6-chlorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0222] 1-(2-fluoro-6-chlorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0223] 1-(2,6-dichlorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0224] 1-(2-bromo-6-chlorophenyl)-4-butyl-1,3-dihydro-3-[2′-1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0225] 1-(2-methoxy-6-chlorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0226] 1-(2-carboxy-6-chlorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0227] 1-(2-acetyl-6-chlorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0228] 1-(2-methyl-6-methoxyphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl) [1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0229] 1-(2-ethyl-6-methoxyphenyl) -d-butyl-1, 3-dihydro-3- [2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0230] 1-(2-propyl-6-methoxyphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′l-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0231]1-(2-isopropyl-6-methoxyphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0232]1-(2-tertbutyl-6-methoxyphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0233] 1-(2-fluoro-6-methoxyphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0234] 1-(2-chloro-6-methoxyphenyl)-4-butyl-1,3-dihydro-3- [2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0235] 1-(2-bromo-6-methoxyphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0236] 1-(2-methoxy-6-methoxyphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0237] 1-(2-carboxy-6-methoxyphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0238] 1-(2-acetyl-6-methoxyphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0239] 1-(2,6-dimethylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0240] 1-(2-ethyl-6-methylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0241] 1-(2-propyl-6-methylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0242] 1-(2-isopropyl-6-methylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0243] 1-(2-tertbutyl-6-methylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0244] 1-(2-fluoro-6-methylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0245] 1-(2-chloro-6-methylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0246] 1-(2-bromo-6-methylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0247] 1-(2-methoxy-6-methylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0248] 1-(2-carboxy-6-methylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0249] 1-(2-acetyl-6-methylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0250] 1-(2-methyl-6-ethylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0251] 1-(2,6-diethylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0252] 1-(2-propyl-6-ethylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0253] 1-(2-isopropyl-6-ethylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0254] 1-(2-tertbutyl-6-ethylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0255] 1-(2-fluoro-6-ethylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0256] 1-(2-chloro-6-ethylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0257] 1-(2-bromo-6-ethylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0258] 1-(2-methoxy-6-ethylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0259] 1-(2-carboxy-6-ethylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0260] 1-(2-acetyl-6-ethylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0261] 1-(2-methyl-6-isopropylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0262] 1-(2-ethyl-6-isopropylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0263] 1-(2-propyl-6-isopropyiphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0264] 1-(2,6-diisopropylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0265] 1-(2-tertbutyl-6-isopropylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0266] 1-(2-fluoro-6-isopropylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0267] 1-(2-chloro-6-isopropylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0268] 1-(2-bromo-6-isopropylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0269] 1-(2-methoxy-6-isopropylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0270] 1-(2-carboxy-6-isopropylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0271] 1-(2-acetyl-6-isopropylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0272] 1-(2-methyl-6-tertbutylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0273] 1-(2-ethyl-6-tertbutylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0274] 1-(2-propyl-6-tertbutylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0275] 1-(2-isopropyl-6-tertbutylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0276] 1-(2,6-ditertbutylphenyl)-4-pentyl-1,3-dihydro-3-[2,-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0277] 1-(2-fluoro-6-tertbutylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0278] 1-(2-chloro-6-tertbutylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2 -one;

[0279] 1-(2-bromo-6-tertbutylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0280] 1-(2-methoxy-6-tertbutylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0281] 1-(2-carboxy-6-tertbutylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2 -one;

[0282] 1-(2-acetyl-6-tertbutylphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0283] 1-(2-methyl-6-fluorophenyl)-4-pentyl-1,3-dihydro-3- 2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0284] 1-(2-ethyl-6-fluorophenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0285] 1-(2-propyl-6-fluorophenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0286] 1-(2-isopropyl-6-fluorophenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0287] 1-(2-tertbutyl-6-fluorophenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0288] 1-(2,6-difluorophenyl)-4-pentyl-1,3-dihydro-3-[2′-1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0289] 1-(2-chloro-6-fluorophenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0290] 1-(2-bromo-6-fluorophenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0291] 1-(2-methoxy-6-fluorophenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0292] 1-(2-carboxy-6-fluorophenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0293] 1-(2-acetyl-6-fluorophenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0294] 1-(2-methyl-6-chlorophenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0295] 1-(2-ethyl-6-chlorophenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0296] 1-(2-propyl-6-chlorophenyl)-4-pentyl-1,3-dihydro-3- [2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0297] 1-(2-isopropyl-6-chlorophenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0298] 1-(2-tertbutyl-6-chlorophenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0299] 1-(2-fluoro-6-chlorophenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0300] 1-(2,6-dichlorophenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0301] 1-(2-bromo-6-chlorophenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0302] 1-(2-methoxy-6-chlorophenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0303] 1-(2-carboxy-6-chlorophenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0304] 1-(2-acetyl-6-chlorophenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0305] 1-(2-methyl-6-methoxyphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0306] 1-(2-ethyl-6-methoxyphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmehyl]-2H-imidazol-2-one;

[0307] 1-(2-propyl-6-methoxyphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0308] 1-(2-isopropyl-6-methoxyphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0309] 1-(2-tertbutyl-6-methoxyphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0310] 1-(2-fluoro-6-methoxyphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0311] 1-(2-chloro-6-methoxyphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0312] 1-(2-bromo-6-methoxyphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0313] 1-(2-methoxy-6-methoxyphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0314] 1-(2-carboxy-6-methoxyphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one; and

[0315] 1-(2-acetyl-6-methoxyphenyl)-4-pentyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1-biphenyl]-4-ylmethyl]-2H-imidazol-2-one.

[0316] A group of specific compounds of more particular interest withinthis second family of more preferred compounds of Formula I consists ofpoly-substituted-phenyl-type compounds, their stereoisomers andtautomers, and the pharmaceutically-acceptable salts thereof, saidcompounds consisting of

[0317] 1-(2,6-dimethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H -tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0318] 1-(2-ethyl-6-methylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0319] 1-(2-propyl-6-methylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0320] 1-(2-isopropyl-6-methylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0321] 1-(2-tertbutyl-6-methylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0322] 1-(2-fluoro-6-methylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0323] 1-(2-chloro-6-methylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0324] 1-(2-bromo-6-methylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0325] 1-(2-methoxy-6-methylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0326] 1-(2-carboxy-6-methylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0327] 1-(2-acetyl-6-methylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0328] 1-(2-methyl-6-ethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0329] 1-(2,6-diethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-irnidazol-2-one;

[0330] 1-(2-propyl-6-ethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0331] 1-(2-isopropyl-6-ethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0332] 1-(2-tertbutyl-6-ethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0333] 1-(2-fluoro-6-ethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0334] 1-(2-chloro-6-ethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0335] 1-(2-bromo-6-ethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0336] 1-(2-methoxy-6-ethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0337] 1-(2-carboxy-6-ethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0338] 1-(2-acetyl-6-ethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0339] 1-(2-methyl-6-isopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0340] 1-(2-ethyl-6-isopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0341] 1-(2-propyl-6-isopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0342] 1-(2,6-diisopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0343] 1-(2-tertbutyl-6-isopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0344] 1-(2-fluoro-6-isopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0345] 1- (2-chloro-6-isopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1-biphenyll-4-ylmethyl]-2H-imidazol-2-one;

[0346] 1-(2-bromo-6-isopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0347] 1-(2-methoxy-6-isopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0348] 1-(2-carboxy-6-isopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0349] 1-(2-acetyl-6-isopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0350] 1-(2-methyl-6-tertbutylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0351] 1-(2-ethyl-6-tertbutylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0352] 1-(2-propyl-6-tertbutylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmetlhyl]-2H-imidazol-2-one;

[0353] 1-(2-isopropyl-6-tertbutylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol -2 -one;

[0354] 1-(2,6-ditertbutylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0355] 1-(2-fluoro-6-tertbutylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0356] 1-(2-chloro-6-tertbutylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0357] 1-(2-bromo-6-tertbutylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0358] 1-(2-methoxy-6-tertbutylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0359] 1-(2-carboxy-6-tertbutylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0360] 1-(2-acetyl-6-tertbutylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0361] 1-(2-methyl-6-fluorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0362] 1-(2-ethyl-6-fluorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0363] 1-(2-propyl-6-fluorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0364] 1-(2-isopropyl-6-fluorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0365] 1-(2-tertbutyl-6-fluorophenyl) -4-butyl-1, 3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0366] 1-(2,6-difluorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0367] 1-(2-chloro-6-fluorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0368] 1-(2-bromo-6-fluorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0369] 1-(2-methoxy-6-fluorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0370] 1-(2-carboxy-6-fluorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0371] 1-(2-acetyl-6-fluorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0372] 1-(2-methyl-6-chlorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0373] 1-(2-ethyl-6-chlorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0374] 1-(2-propyl-6-chlorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0375] 1-(2-isopropyl-6-chlorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0376] 1-(2-tertbutyl-6-chlorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0377] 1-(2-fluoro-6-chlorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0378] 1-(2,6-dichlorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0379] 1-(2-bromo-6-chlorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol -5-yl)[1,1-biphenyl]-4-ylmethyl]-2H-imidazoi-2-one;

[0380] 1-(2-methoxy-6-chlorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0381] 1-(2-carboxy-6-chlorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0382] 1-(2-acetyl-6-chlorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0383] 1-(2-methyl-6-methoxyphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0384] 1-(2-ethyl-6-methoxyphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0385] 1-(2-propyl-6-methoxyphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0386] 1-(2-isopropyl-6-methoxyphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0387] 1-(2-tertbutyl-6-methoxyphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0388] 1-(2-fluoro-6-methoxyphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0389] 1-(2-chloro-6-methoxyphenyl) -4-butyl-1,3-dihydro-3- [2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0390] 1- (2-bromo-6-methoxyphenyl) -4-butyl-1,3-dihydro-3- [2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0391] 1-(2-methoxy-6-methoxyphenyl) -4-butyl-l,3-dihydro-3- [2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;

[0392] 1-(2-carboxy-6-methoxyphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl) [1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one; and

[0393] 1-(2-acetyl-6-methoxyphenyl) -4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one.

[0394] The term “hydrido” denotes a single hydrogen atom (H) . Thishydrido group may be attached, for example, to an oxygen atom to form ahydroxyl group; or, as another example, one hydrido group may beattached to a carbon atom to form a

[0395] group; or, as another example, two hydrido groups may be attachedto a carbon atom to form a —CH₂— group. Where the term “alkyl” is used,either alone or within other terms such as “haloalkyl”, the term“alkyll” embraces linear or branched radicals having one to about twentycarbon atoms or, preferably, one to about twelve carbon atoms. Morepreferred alkyl radicals are “lower alkyl” radicals having one to aboutten carbon atoms. most preferred are lower alkyl radicals having one toabout five carbon atoms. The term “cycloalkyl” embraces cyclic radicalshaving three to about ten ring carbon atoms, preferably three to aboutsix carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl andcyclohexyl. The term “haloalkyl” embraces radicals wherein any one ormore of the alkyl carbon atoms is substituted with one or more halogroups, preferably selected from bromo, chloro and fluoro. Specificallyembraced by the term “haloalkyl” are monohaloalkyl, dihaloalkyl andpolyhaloalkyl groups. A monohaloalkyl group, for example, may haveeither a bromo, a chloro, or a fluoro atom within the group. Dihaloalkyland polyhaloalkyl groups may be substituted with two or more of the samehalo groups, or may have a combination of different halo groups. Adihaloalkyl group, for example, may have two fluoro atoms, such asdifluoromethyl and difluorobutyl groups, or two chloro atoms, such as adichloromethyl group, or one fluoro atom and one chloro atom, such as afluoro-chloromethyl group. Examples of a polyhaloalkyl aretrifluoromethyl, 1,1-difluoroethyl, 2,2,2-trifluoroethyl, perfluoroethyland 2,2,3,3-tetrafluoropropyl groups. The term “difluoroalkyl” embracesalkyl groups having two fluoro atoms substituted on any one or two ofthe alkyl group carbon atoms. The term “alkoxy” embraces linear orbranched oxy-containing radicals having alkyl portions of one to aboutten carbon atoms, such as methoxy group. The term “alkoxyalkyl” alsoembraces alkyl radicals having two or more alkoxy groups attached to thealkyl radical, that is, to form monoalkoxyalkyl and dialkoxyalkylgroups. The terms “alkylcarbonyl” and “acyl” are interchangeable. Anexample of “alkylcarbonyl” is “acetyl”. The terms “benzyl” and“phenylmethyl” are interchangeable. For any of the foregoing definedradicals, preferred radicals are those containing from one to about tencarbon atoms.

[0396] Specific examples of alkyl groups are methyl, ethyl, n-propyl,isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl,isopentyl, methylbutyl, dimethylbutyl and neopentyl.

[0397] Compounds of Formula I have been found to inhibit the action ofangiotensin II in mammals. Angiotensin II is a potent vasoconstrictorand participates in the formation of aldosterone which regulates sodiumand water balance in mammals. Thus, compounds of Formula I aretherapeutically useful in methods for treating hypertension byadministering to a hypertensive patient a therapeutically-effectiveamount of a compound of Formula I. The phrase “hypertensive patient”means, in this context, a mammalian subject suffering from or afflictedby the effects of hypertension or susceptible to a hypertensivecondition if not treated to prevent or control such hypertension.

[0398] Also included in the family of compounds of Formula I areisomeric forms including diastereoisomers and thepharmaceutically-acceptable salts thereof. The term“pharmaceutically-acceptable salts” embraces salts commonly used to formalkali metal salts and to form addition salts of free acids or freebases. The nature of the salt is not critical, provided that it ispharmaceutically-acceptable. Suitable pharmaceutically-acceptable acidaddition salts of compounds of Formula I may be prepared from aninorganic acid or from an organic acid. Examples of such inorganic acidsare hydrochloric, hydrobromic, hydroiodic, nitric, carbonic, sulfuricand phosphoric acid. Appropriate organic acids may be selected fromaliphatic, cycloaliphatic, aromatic, araliphatic, heterocyclic,carboxylic and sulfonic classes of organic acids, example of which areformic, acetic, propionic, succinic, glycolic, gluconic, lactic, malic,tartaric, citric, ascorbic, glucuronic, maleic, fumaric, pyruvic,aspartic, glutamic, benzoic, anthranilic, p-hydroxybenzoic, salicyclic,phenylacetic, mandelic, embonic (pamoic), methansulfonic,ethanesulfonic, 2-hydroxyethanesulfonic, pantothenic, benzenesulfonic,toluenesulfonic, sulfanilic, mesylic, cyclohexylaminosulfonic, stearic,algenic, b-hydroxybutyric, malonic, galactaric and galacturonic acid.Suitable pharmaceutically-acceptable base addition salts of compounds ofFormula I include metallic salts made from aluminium, calcium, lithium,magnesium, potassium, sodium and zinc or organic salts made fromN,N′-dibenzylethylenediamine, chloroprocaine, choline, diethanolamine,ethylenediamine, meglumine (N-methylglucamine) and procaine. All ofthese salts may be prepared by conventional means from the correspondingcompound of Formula I by reacting, for example, the appropriate acid orbase with the compound of Formula I.

GENERAL SYNTHETIC PROCEDURES

[0399] Compounds embraced by Formula I may be prepared in accordancewith Schemes I-VIII, which follow, wherein the R substituents are asdefined for Formula I, above, except where further noted.

[0400] Synthetic Scheme I shows the preparation of the alkylating agent1 where R⁵ equal CN₄C(C₆H₅)₃ from the corresponding methyl ester 2(R⁵=CO₂CH₃). In step 1, the methyl ester is converted to thecorresponding acid (R⁵=CO₂H) by the action of sodiumhydroxide/hydrochloric acid. In step 2, the acid is converted to thecorresponding acid chloride (R⁵=COCl) by the action of oxalyl chloride.In step 3, the acid chloride is converted to the corresponding primaryamide (R⁵=CONH₂) by the action of ammonia. In step 4, the amide isconverted to the corresponding nitrile 3 by the action of thionylchloride at reflux. In step 5, the nitrile 3 is reacted withtrimethyltinazide in xylene at reflux to give the correspondingtrimethytin protected tetrazole 4. In step 5, 6, and 7 deprotection withacetic acid/water and reprotection with triphenylmethylchloride/triethylamine gives the N-trityltetrazole 5 (R⁵=CN₄C(C₆H₅)₃).In step 8, bromination with N-bromosuccinimide (NBS) provides theN-trityltetrazole alkylating agent 1.

[0401] Synthetic Scheme II shows the preparation of N-Boc-amino ketones6 (or aldehydes when R⁴ =H) from the corresponding N-Boc-amino acides 7.In step 1, the amino acid 7 is reacted with isobutyl chloroformate inthe presence of triethylamine and subsequently withN,O-dimethylhydroxylamine to give the correspondingN-methoxy-N-methylamide 8. In step 2, the amide 8 is reacted with anorganolithium reagent R⁴−Li (or lithium aluminum hydride (LAH) whenR⁴=H) to give the desired ketone 6 (or aldehyde when R⁴=H).

[0402] Synthetic Scheme III shows the preparation of imidazol-2-ones 9from the corresponding amides 8 via Method A. In step 1, the protectedamide 8 (prepared in Scheme II) is reacted with trifluoroacetic acid(TFA) to give the TFA salt 10 of the free amine. In step 2, the salt 10is reacted with the appropriate isocyanate 11 in the presence oftriethylamine to give the urea 12. In step 3, the urea 12 is reactedwith an organolithium reagent R⁴−Li (or lithium aluminum hydride (LAH)when R⁴=H) and subsequently cyclized to the imidazole-2-one 9 ontreatment with dilute acid during the work-up procedure.

[0403] Synthetic Scheme IV shows the preparation of imidazol-2-ones 9from the corresponding N-Boc-protected amino ketones 6 (or aldehydeswhen R⁴=H) via Method B. In step 1, the carbonyl compound 6 (prepared inScheme II) is reacted with anhydrous hydrogen chloride in dioxane togive the HCl salt 13. In step 2, the salt 13 is reacted with theappropriate isocyanate 11 in chloroform to give the imidazol-2-one 9directly.

[0404] Synthetic Scheme V shows the preparation of imidazol-2-ones 9from the corresponding N-Boc-protected amino ketones 6 (or aldehydeswhen R⁴=H) via Method C. In step 1, the carbonyl compound 6 (prepared inScheme II) is reacted with 2,2-dimethyl-1,3-propandiol to give thecyclic ketal 14. In step 2, the ketal 14 is reacted with TFA to give theTFA salt 15 of the free amine. In step 3, the salt 15 is reacted withthe appropriate isocyanate 11 in the presence of triethylamine to givethe urea ketal 16. In step 4, the urea keral 16 is reacted with 6Nhydrochloric acid at 60° C. to give the desired imidazol-2-one 9directly.

[0405] Synthetic Scheme VI shows the preparation ofbiphenylmethylimidazol-2-ones 17 from the parent imidazol-2-ones 9(prepared in Scheme III, Scheme IV, or Scheme V). In step 1, theimidazol-2-one 9 is first treated with a base, such as potassiumt-butoxide, and subsequently with the alkylating agent 1 (prepared inScheme I) to give the protected coupled imidazol-2-one 18. In step 2,the N-trityl (triphemylmethyl) protected 8 is deprotected with aceticacid/water to give the desired angiotensin II antagonist 17.

[0406] Synthetic Scheme VII shows the preparation of substitutedbenzylimidazol-2-ones 19 from the TFA salt of the amino amide 10(prepared in Scheme II). In step 1, the TFA salt 10 is allowed to reactwith the substituted benzaldehyde 20 in the presence of triethylamineand anhydrous magnesium sulfate to give the imine 21. In step 2, theimine 21 is allowed to react with sodium borohydride to give thesubstituted benzylamine 22. In step 3, the benzylamine 22 is allowed toreact with the appropriate isocyanate 11 to give the substitutedbenzylurea 23. In step 4, the urea 23 is first allowed to react with anorganolithium reagent R⁴−Li (or lithium aluminum hydride (LAH) whenR⁴=H) and subsequently with dilute aqueous acid to give the desiredsubstituted benzylimidazol-2-one 19.

[0407] Synthetic Scheme VIII shows the preparation ofbiphenylmethylimidazol-2-ones 17 from 4-bromobenzylimidazol-2-ones 19(prepared in Scheme VII). In step 1, the bromobenzylimidazol-2-one 19 isallowed to react with the boronic acid amide 24 (which can be preparedfrom N-t-butyl-N-methylbenzamide via ortho metalation) in the presenceof a palladium catalyst, such as tetrakis(triphenylphospine) palladium,to give the biphenylmethylimidazol-2-one amide 25. In step 2, theN-t-butyl-N-methylamide 25 is allowed to react with TFA to give theN-methylamide, sodium nitrite to give the N-nitrosoamide, and ethanolicpotassium hydroxide to give the biphenylmethylimidazol-2-one carboxylicacid 26. In step 3, the acid 26 is allowed to react with oxalyl chlorideto give the acid chloride, anhydours ammonia to give the primary amide,triphenylphospine/carbon tetrachloride to give the nitrile, and aceticacid/water to give the desired angiotensin II antagonist 17.

[0408] The following Examples 1-9 contain detailed descriptions of themethods of preparation of compounds of Formula I. These detaileddescriptions fall within the scope of, and serve to exemplify, the abovedescribed General Synthetic Procedures which form part of the invention.These detailed descriptions are presented for illustrative purposes onlyand are not intended as a restriction on the scope of the invention. Allparts are by weight and temperatures are in degrees Centigrade, unlessotherwise indicated.

EXAMPLE 1

[0409]

[0410] 1-(2-ethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one

[0411] Step 1: Preparation ofN-Triphenylmethyl-5-[2-(4′-bromomethylbiphen -2-yl]tetrazole.

[0412] A 542.5 g (2.4 mol) sample of methyl 2-(p-tolyl)benzoate (ChemoDynamics Inc.) was dissolved in 5.5 L of ethanol and treated with 3 L(7.5 mol) of 2.5 N sodium hydroxide. The reaction was stirred overnightat ambient temperature and treated with an additional 480 ml (6.0 mol)of sodium hydroxide; stirring was continued for an additional 24 h andthe ethanol removed in vacuo. The remaining solution was cooled in iceand acidified to pH 1 with hydrochloric acid which caused the product toprecipitate; filtration and drying in vacuo gave 510 g (100%) of crude2-(p-tolyl)benzoic acid: mp 145.0-147.5° C.; NMR (CDCl₃) δ2.40 (s, 3H) ,7.17-7.28 (m, 4H), 7.35-7.45 (m, 2H), 7.51-7.59 (m, 1H), 7.90-7.97 (m,1H). The crude acid was suspended in 1 L of toluene and slowly treatedwith 400 g (3.15 mol) of oxalyl chloride under nitrogen. The reactionwas allowed to stir at ambient temperature for 4.5 h and concentrated invacuo to remove excess oxalyl chloride. The residue was redissolved in 2L of toluene and treated with 92.8 g (5.46 mol) of anhydrous ammonia.The reaction was filtered and the filtrate concentrated in vacuoproducing 424 g (84%) of crude 2-(p-tolyl)benzamide: mp 128-130° C.; NMR(CDCl₃) δ2.40 (s, 3H), 5.28 (br s, 1H), 5.77 (br s, 1H), 7.21-7.53 (m,7H), 7.76-7.83 (m, 1H). The crude amide was treated with 1420 ml (19.5mol) of thionyl chloride at reflux for 3.5 h. The reaction was filteredand the thionyl chloride removed in vacuo. The residue was dissolved in800 ml of toluene and reconcentrated in vacuo. On standing overnight,the residue crystallized. The crystals were collected and washed withhexane to give 296 g (64%) of 2-(p-tolyl)benzonitrile: mp 50.5-52.0° C.;NMR (CDCl₃) δ2.42 (s, 3H), 7.22-7.34 (m, 2H), 7.37-7.52 (m, 3H),7.58-7.66 (m, 1H), 7.72-7.78 (m, 1H). A 286 g (1.48 mol) sample of thecrude nitrile was dissolved in 1630 mL to toluene and treated with 377 g(1.8 mol) of trimethyltinazide at reflux for 24 h. The reaction wascooled; filtration gave 600 g of crudeN-trimethylstannyl-5-[2-(4′-methylbiphen-2-yl]tetrazole: mp 271-272° C.(dec.); NMR (DMSO-d₆) δ0.36 (br t, J═34 Hz, 9H), 2.24 (s, 3H), 6.89-7.06(m, 4H), 7.35-7.55 (m, 4H). The crude N-trimethylstannyl tetrazole wassuspended in 4270 mL of toluene and 287 mL of anhydrous tetrahydrofuran(THF) and treated with 6.34 g (173 mol) of anhydrous hydrogen chlorideat ambient temperature under nitrogen with stirring. The reaction wasallowed to stand overnight and filtered; recrystallization from toluenegave 217 g (62%) of 5-[2-(4′-methylbiphen-2-yl)]tetrazole as a solid: mp149-152° C.; NMR (DMSO-d₆) δ2.28 (s, 3H), 6.94-7.02 (m, 2H), 7.08-7.15(m, 2H), 7.50-7.59 (m, 2H), 7.62-7.72 (m, 2H). A 200 g (0.85 mol) sampleof the tetrazole was suspended in 3.3 L of dichloromethane and treatedwith 262 g (0.91 mol) of triphenylmethyl chloride and 141 mL (1.0 mol)of anhydrous triethylamine. The reaction was stirred at reflux for 3 hunder nitrogen, washed with water, dried (MgSO₄), and concentrated invacuo. Recrystallization gave 338 g (83%) ofN-triphenylmethyl-5-[2-4′-methylbiphen-2-yl)]tetrazole as a colorlesssolid: mp 170-173° C.; NMR (CDCl₃) δ2.27 (s, 3H) , 6.86-6.96 (m, 8H),6.98-7.04 (m, 2H), 7.09-7.52 (m, 12H), 7.86-7.94 (m, 1H). TheN-triphenylmethyl tetrazole was dissolved in 4260 mL of carbontetrachloride and treated with 126.4 g (0.71 mol) of N-bromosuccinimide(NBS) of 11.9 g (49 mmol) of benzoyl peroxide at reflux for 3.5 h. Thereaction was filtered and the solvent removed in vacuo.Recrystallization from toluene gave 277 g (59%) of N′triphenylmethyl-5-[2-4′-bromomethylbiphen-2-yl)]tetrazole as a colorlesssolid: mp 140-142° C.; NMR (CDCl) δ4.39 (s, 2H) , 6.85-6.95 (m, 7H) ,7.06-7.15 (m, 4H), 7.22-7.43 (m, 9H), 7.45-7.55 (m, 2H), 7.94-8.01 (m,1H). NMR indicated that this material was only 85% pure; it contained 7%of corresponding dibromocompound (δ6.50) and 8% of starting material(δ2.27); however, no further attempts at purification were made and thismixture was used as is for the subsequent alkylation reaction.

[0413] Step 2: Preparation ofN-t-Boc-L-norleucine-N-methoxy-N-methylamide.

[0414] Under nitrogen, a stirred solution of 70.25 g (0.3 mol) ofN-t-Boc-norleucine and 30.8 g (0.3 mol) of triethylamine (TEA) in 750 mLof dichloromethane (DCM) at −15° C. was treated with 44.2 g (0.32 mol)of isobutyl chlorformate. After 15 min, a slurry of 32.6 g (0.33 mol) ofN,O-dimethylhydroxylamine in 100 mL of DCM was added followed by 33.8 g(0.33 mol) of TEA at such a rate as to maintain the reaction temperatureat −5° C. The reaction was stirred at −10° C. for 1 h and then allowedto warm to ambient temperature and stir overnight. The reaction wasdiluted with 1 L of chloroform and washed with 1 M citric acid, NaHCO₃(sat), and brine. The solution was dried (Na₂SO₄) and concentrated invacuo to give 80.2 g of crude product as a yellow oil. Purification bysilica gel chromatography (Waters Prep-500A) using ethyl acetate/hexane(75:25) gave 58.1 g (74%) of colorless product as an oil: NMR (CDCl₃)δ0.88 (t, J=7 Hz, 3H), 1.28-1.38 (m, 4H), 1.43 (S, 9H), 1.49-1.57 (m,1H), 1.63-1.75 (m, 1H), 3.20 (S, 3H), 3.76 (s, 3H), 4.60-4.72 (m, 1H),5.13 (d, J=8 Hz, 1H).

[0415] Step 3: Preparation of L-norleucine-N-methoxy-N-methylamide.

[0416] Under nitrogen, 50 g (182 mmol) of N-t-Boc-L-norleucine-N-methoxy-N-methylamide from Step 2 was dissolved in 25 mL of methylenechloride and treated with 75 mL of anhydrous trifluoroacetic acid (TFA).The mixture was stirred at ambient temperature overnight andconcentrated in vacuo. The residue was dissolved in 1 M Na₂CO₃ andcontinuously extracted with ether to afford 29.1 g (66%) ofL-norleucine-N-methoxy-N-methylamide as a colorless oil: NMR (CDCl₃)δ0.75 (s, 3H), 1.10-1.35 (m, 4H), 1.74-1.85 (m, 2H), 3.04 (s, 3H), 3.55(S, 3H), 3.70-3.79 (m, 1H).

[0417] Step 4: Preparation of 1-(2-ethylphenyl)-4-butyl-1,3-dihydro-2H-imidazol-2-one.

[0418] Under nitrogen, a solution of 4.86 g (30 mmol) of carbonyldiimidazole in 50 mL of methylene chloride was treated with 3.63 g (30mmol) of 2-ethylaniline (Aldrich). The reaction was allowed to stir atambient temperature for 90 min prior to the addition of 4.80 g (30 mmol)of L-norleucine-N-methoxy-N-methylamide from Step 3. The reaction wasstirred overnight, filtered and concentrated in vacuo. Purification bysilica gel chromatography (Waters Prep-500A) using ethylacetate/hexane(40:60) gave 2.45 g (25%) of the 2-ethylphenyl urea ofL-norleucine-N-methoxy-N-methylamide as a colorless solid: NMR (CDCl₃)δ0.88 (t, J=7 Hz, 3H), 1.14 (t, J=8 Hz, 3H), 1.30-1.38 (m, 2H),1.38-1.60 (m, 2H), 1.63-1.80 (m, 2H), 2.49 (t, J=7 Hz, 2H), 2.56 (t, J=8Hz, 2H), 3.20 (s, 3H), 3.82 (s, 3H), 4.18-4.27 (m, 1H), 4.96 (5, J=8 Hz,1H), 6.77 (br s, 1H), 7.05-7.22 (m, 2H), 7.32-7.43 (m, 1H), 7.54 (d, J=8Hz, 1H). A solution of 2.37 g (7.4 mmol) of this urea in 50 mL ofanhydrous THF/ether (1:1) was treated with 9.2 mL (9.2 mmol) of 1M LAHin ether at ambient temperature. The reaction was allowed to stir for 90min and was slowly treated with a solution of 1.77 g (13 mmol) of KHSO₄in 45 mL of water. This mixture was rapidly stirred for 3 hr and thenthe layers were separated. The aqueous layer was extracted three timeswith ether and the extracts were combined with the organic layer. Theetheral solution was washed with brine, dried (MgSO₄), and concentratedin vacuo. The residue was dissolved in 30 mL of methylene chloride,treated with 0.5 mL of TFA, and stirred at reflux for 3 hr. The reactionwas cooled to ambient temperature, washed with NaHCO₃ (sat), dried(MgSO₄), and concentrated in vacuo to give 1.8 g (100%) of1-(2-ethylphenyl)-4-butyl-1,3-dihydro-2H-imidazol-2-one as a colorlessoil: NMR (CDCl₃) δ0.92 (t, J=7 Hz, 3H), 1.17 (t, J=7, Hz, 3H), 1.38 (m,J=7 Hz, 2H), 1.58 (m, J=7 Hz, 2H), 2.46 (t, J=7 Hz, 2H), 2.58 (q, J=7Hz, 2H), 6.06 (s, 1H), 7.16-7.30 (m, 2H), 7.30-7.40 (m, 2H).

[0419] Step 5: Preparation of 1-(2-ethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-bithenyl]-4-ylmethyl]-2H-imidazol-2-one.

[0420] Under nitrogen, a solution of 1.8 g (7.4 mmol) of theimidazol-2-one from Step 4 in 75 mL of anhydrous dimethylforamide (DMF)was cooled to −63° C. (CHCl₃/CO₂) and treated with 7.4 mL (7.4 mmol) of1 M potassium tert-butoxide in THF. The anion solution was then treatedwith 5.17 g (7.4 mmol) of solidN-triphenylmethyl-5-[2-(4′bromomethylbiphen -2-yl]tetrazole from Step 1at such a rate to maintain the reaction temperature below −55° C. Afterthe addition was complete, the reaction was allowed to slowly warm toambient temperature overnight, quench with 10 mL of water, andconcentrated in vacuo. The residue was dissolved in ethyl acetate whichwas washed with water, dried (MgSO₄), and reconcentrated in vacuo togive the crude product. Purification by silica gel chromatography(Waters Prep-500A) using ethyl acetate/hexane (30:70) gave 1.10 g (15%)of pure trityl-protected coupled product which was stirred in 20 mL ofacetic acid/water (90:10) for 3 days. All volitiles were removed invacuo and the residue recrystallized from acetonitrile to give 535 mg(73%) of 1-(2-ethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-oneas a colorless solid: mp 188-189° C.; NMR (CDCl₃) δ0.82 (t, J=7 Hz, 3H)0.97 (t, J=8 Hz, 3H), 1.23-1.35 (m, 2H), 1.36-1.48 (m, 2H), 2.26 (t, J=7Hz, 2H), 2.37 (q, J=8 Hz, 2H), 4.75 (s, 2H), 5.95 (s, 1H), 6.98-7.15 (m,7H), 7.36-7.58 (m, 4H), 7.79 (dd, J=8 and 2 Hz, 1H); MS (FAB) m/e (relintensity) 479 (12), 277 (8), 243 (18), 185 (100), 149 (8); HRMS. Calc'dfor M+H: 479.2560. Found: 479.2590.

EXAMPLE 2

[0421]

[0422] 1-(2-isopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one

[0423] Step 1: Preparation of 1-(2-isopropylphenyl)-4-butyl-1.3-dihydro-2H-imidazol-2-one.

[0424] Following General Synthetic Scheme III, 1-(2-isopropylphenyl)-4-butyl-1,3-dihydro-2H-imidazol-2-one was prepared: NMR (CDCl₃) δ0.89(t, J=7 Hz, 3H), 1.21 (d, J=7 Hz, 6H), 1.30-1.44 (m, 2H), 1.48-1.60 (m,2H), 2.38 (t, J=7 Hz, 2H), 3.05 (m, J=7 Hz, 1H), 5.93-5.96 (m, 1H),7.17-7.42 (m, 4H), 10.65 (br s, 1H); MS (FAB) m/e (rel intensity) 259(100); HRMS. Calc'd for M+H: 259.1810. Found: 259.1799.

[0425] Step 2: Preparation of1-(2-isopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one.

[0426] Following General Synthetic Scheme VI, the imidazol-2-one fromStep 1 was converted to1-(2-isopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-oneas a colorless solid: mp 167-168° C.; NMR (CDC₃) δ0.82 (t, J=7 Hz, 3H),0.99 (d, J=8 Hz, 6H), 1.22-1.34 (m, 2H), 1.35-1.49 (m, 2H), 2.27 (t, J=7Hz, 2H), 2.77 (m, J=8 Hz, 1H), 4.74 (s, 2H), 5.95 (s, 1H), 6.98 (d, J=3Hz, 1H) , 7.03 (d, J=8 Hz, 2H), 7.10 (d, J=8 Hz, 2H), 7.14-7.24 (m, 2H),7.35-7.56 (m, 4H), 7.76 (d, J=8 Hz, 1H). MS (FAB) m/e (rel intensity)493 (18), 207 (100), 178 (19), 130 (5); HRMS. Calc'd for M+H: 493.2716.Found: 493.2684.

EXAMPLE 3

[0427]

[0428] 1-(2,6-dimethoxyphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one

[0429] Step 1: Preparation of1-(2,6-dimethoxyhenyl)-4-butyl-1,3-dihydro-2H-imidazol-2-one.

[0430] Following General Synthetic Scheme III, 1-(2,6-dimethylyphenyl)-4-butyl-1,3-dihydro-2H-imidazol-2-one was prepared: NMR (DMSO-d₆) δ0.89(t, J=8 Hz, 3H), 1.27-1.40 (m, 2H), 1.42-1.57 (m, 2H), 2.26 (t, J=8 Hz,2H), 3.71 (s, 6H), 5.91 (t, J=l Hz, 1H), 6.72 (d, J=8 Hz, 2H), 7.31 (t,J=8 Hz, 2H), 9.85 (br s, 1H).

[0431] Step 2: Preraration of1-(2,6-dimethoxyphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one.

[0432] Following General Synthetic Scheme VI, the imidazol-2-one fromStep 1 was converted to 1-(2,6-dimethoxyphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-oneas a colorless solid: mp 189-191° C. (dec); NMR (DMSO-d6) δ0.81 (t, J=7Hz, 3H), 1.20-1.44 (m, 4H), 2.22 (t, J=7 Hz, 2H), 3.74 (s, 6H) , 4.80(s, 2H) , 6.07 (s, 1H) , 6.76 (d, J=8 Hz, 2H), 7.08 (d, J=8 Hz, 2H),7.13 (d, J=8 Hz, 2H), 7.34 (t, J=8 Hz, 1H), 7.53-7.61 (m, 2H), 7.62-7.73(m, 2H). MS (FAB) m/e (rel intensity) 511 (20); HRMS. Calc'd for M+H:511.2458, Found: 511.2527.

EXAMPLE 4

[0433]

[0434] 1- (2-chloro-6-methylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmerhyl]-2H -imidazol-2-one

[0435] Step 1: Preparation of 1-(2-chloro-6-methylphenyl) -4-butyl-1,3-dihydro-2H-imidazol-2-one.

[0436] Following General Synthetic Scheme III,1-(2-chloro-6-methylphenyl) -4-butyl-1,3-dihydro-2H-imidazol-2-one wasprepared: NMR (CDCl₃) δ0.90 (t, J=7 Hz, 3H) , 1.35 (m, J=7 Hz, 2H) ,1.55 (m, J=7 Hz, 2H) , 2.26 (s, 3H) , 2.40 (t, J=7 Hz, 2H) , 5.85-5.88(m, 1H) , 7.17-7.25 (m, 2H), 7.33 (dd, J=7 and 2 Hz, 1H), 10.20 (br s,1H); MS (FAB) m/e (rel intensity) 265 (100), 249 (3), 221 (10), 201 (2),187 (8); HMRS: Calc'd for M+H: 265.1108. Found: 265.1126.

[0437] Step 2: Preparation of 1-(2-chloro-6-methylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one.

[0438] Following Feneral Synthetic Scheme VI, the imidazol-2-one fromStep 1 was converted to 1-(2-chloro-6-methylpheny)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl][1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-oneas a colorless solid: mp 163-164° C.; NMR (CDCl₃) δ0.83 (t, J=7 Hz, 3H),1.21-1.35 (m, 2H), 1.36-1.50 (m, 2H), 2.03 (s, 3H), 2.26 (t, J=8 Hz,2H), 4.68 (d, J=16 Hz, 1H), 4.87 (d, J=16 Hz, 1H), 6.94 (dd, J=7 and2Hz, 1H), 7.00-7.08 (m, 4H), 7.12-7.17 (m, 2H), 7.26-7.33 (m, 1H) ,7.40-7.51 (m, 2H), 7.54-7.61 (m, 2H), 7.77 (dd, J=8 and 1 Hz, 1H); MS(FAB) m/e (rel intensity) 499 (15), 456 (3), 265 (4), 207 (100), 192(24), 178 (21); HRMS: Calc'd for M+H: 499.2013. Found 499.2011.

EXAMPLE 5

[0439]

[0440]1-(2,6-dimethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one

[0441] Step 1: Preparation of1-(2,6-dimethylphenyl)-4-butyl-1,3-dihydro-2H-imidazol-2-one.

[0442] Following General Synthetic Scheme III, 1-(2,6-dimethylphenyl)-4-butyl-1,3-dihydro-2H-imidazol-2-one was prepared: NMR (CDCl₃) δ0.91(t, J=7 Hz, 3H), 1.29-1.32 (m, 2H), 1.49-1.61 (m, 2H), 2.18 (s, 6H),2.41 (t, J=7 Hz, 2H), 5.83-5.86 (m, 1H), 7.07-7.21 (m, 3H), 9.66 (br s,1H); MS (FAB) m/e (rel intensity) 245 (100), 215 (4), 118 (9); HMRS:Calc'd for M+H: 245.1654. Found 245.1668.

[0443] Step 2: Preparation of1-(2,6-dimethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one.

[0444] Following General Synthetic Scheme VI, the imidazol-2-one fromStep 1 was converted to 1-(2,6-dimethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one as a colorless solid: mp177-178° C. (dec); NMR (CDCl₃) δ0.83 (t, J=8 Hz, 3H), 1.22-1.33 (m, 2H),1.34-1.47 (m, 2H), 1.92 (s, 6H), 2.25 (t, J=8 Hz, 2H), 4.76 (s, 2H),5.82 (s, 1H), 6.76 (d, J=8 Hz, 2H), 6.96 (t, J=8 Hz, 1H), 7.04 (d, J=8Hz, 2H), 7.15 (d, J=8 Hz, 2H), 7.42-7.62 (m, 3H) 7.74 (dd, J=8 and 2 Hz,1H); MS (FAB) m/e (rel intensity) 479 (23), 207 (60); HRMS. Calc'd forM+H: 479.2559. Found: 479.2500.

EXAMPLE 6

[0445]

[0446] 1-(2, 6-diethylphenyl) -4-butyl-1,3-dihydro-3- [2′-(1H-tetrazol-5-yl) [1,1′-biphenyl]-4-ylmethyl]-2H-imidazol- 2-one

[0447] Step 1: Preparation of (1,2,6-diethylohenyl)-4-butyl-1,3-dihydro-2H-imidazol-2-one.

[0448] Following General Synthetic Scheme III, 1-(2,6-diethylphenyl)-4-butyl-1,3-dihydro-2H-imidazol-2-one was prepared: NM (CDCl₃) δ0.89(t, J=7 Hz, 3H), 1.17 (t, J=7 Hz, 6H) , 1.33 (m, J=7 Hz, 2H) , 1.53 (m,J=8 Hz, 2H), 2.40 (t, J=7 Hz, 2H) , 2.50 (q, J=8 Hz, 2H) , 2.52 (q, J=8Hz, 2), 5.82-5.84 (m, 1H), 7.16 (d, J=8 Hz, 2H), 7.26-7.33 (m, 1H),10.71 (br s, 1H); MS (FAB) m/e (rel intensity) 273 (100), 255 (15);HRMS: Calc'd for M+H: 273.1967. Found: 273.1980.

[0449] Step 2: Preparation of1-(2,6-diethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-binhenyl]-4-ylmethyl]-2H-imidazol-2-one.

[0450] Following General Synthetic Scheme VI, the imidazol-2-one fromStep 1 was converted to1-(2,6-diethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-oneas a colorless solid: mp 198-200° C. (dec); NMR (CDCl₃) δ0.83 (t, J=7Hz, 3H), 0.95 (t, J=8Hz, 6H) 1.22-1.34 (m, 2H), 1.35-1.48 (m, 2H),2.20-2.32 (m, 6H), 4.75 (s, 2H), 5.85 (s, 1H); 6.84 (d, J=8Hz, 2H), 7.02(d, J=8 Hz, 2H), 7.10 (t, J=8 Hz, 1H), 7.15 (d, J=8 Hz, 2H), 7.41-7.53(m, 2H), 7.54-7.61 (m, 1H), 7.71 (d, J=8Hz, 1H); MS (FAB) m/e (relintensity) 507 (100), 479 (6), 464 (10); HRMS: Calc'd for M+H: 507.2872.Found: 507.2853.

EXAMPLE 7

[0451]

[0452]1-(2,6-diisopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one

[0453] Step 1: Preparation of 1-(2,6-diisopropylphenyl)-4-butyl-1,3-dihydro-2H-imidazol-2-one.

[0454] Following General Synthetic Scheme III, 1-(2,6-diisopropylphenyl)-4-butyl-1,3-dihydro-2H-imidazol-2-one was prepared: NMR (CDCl₃) δ0.92(t, J=8 Hz, 3H), 1.16 (d, J=8 Hz, 6H), 1.23 (d, J=8 Hz, 6H), 1.29-1.44(m, 2H), 1.50-1.61 (m, 2H), 2.41 (t, J=8 Hz, 2H), 2.75-2.91 (m, 2H),5.85 (t, J=1 Hz, 1H), 7.22 (d, J=8 Hz, 2H), 7.36 (t, J=8 Hz, 1H).

[0455] Step 2: Preparation of 1-(2,6-diisopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one.

[0456] Following General Synthetic Scheme VI, the imidazol-2-one fromStep 1 was converted to 1-(2,6-diisopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one as a colorlesssolid: mp 202-203° C. (dec); NMR (CDCl₃) δ0.86 (t, J=7 Hz, 3H), 0.99 (d,J=7 Hz, 6H), 1.08 (d, J=7 Hz, 6H), 1.25-1.52 (m, 4H), 2.32 (t, J=8 Hz,2H), 2.63 (m, J=7Hz, 2H), 4.75 (s, 2H), 5.90 (s, 1H), 7.01-7.12 (m, 6H),7.29 (t, J=8 Hz, 1H), 7.37-7.48 (m, 2H), 7.54 (dt, J=8 and 2 Hz, 1H),7.70 (dd, J=8 and 2 Hz, 1H); MS (FAB) m/e (rel intensity) 535 (22), 207(100), 178 (33); HRMS. Calc'd for M+H: 535.3185. Found: 535.3168.

EXAMPLE 8

[0457]

[0458]1-(2,4,6-trimethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one

[0459] Step 1: Preparation of 1-(2,4,6-trimethylphenyl)-4-butyl-1,3-dihydro-2H-imidazol-2-one.

[0460] Following General Synthetic Scheme III, 1-(2,4,6-trimethylphenyl)-4-butyl-1,3-dihydro-2H-imidazol-2-one was prepared: NMR (CDCl₃) δ0.91(t, J=8 Hz, 3H), 1.28-1.42 (m, 2H), 1.47-1.60 (m, 2H), 2.14 (s, 6H),2.30 (s, 3H), 2.40 (t, J=8 Hz, 2H), 5.80-5.83 (m, 1H), 6.93 (s, 2H),10.20 (br s, 1H).

[0461] Step 2: Preparation of 1-(2,4,6-trimethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one.

[0462] Following General Synthetic Scheme VI, the imidazol-2-one fromStep 1 was converted to 1-(2,4,6-trimethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-oneas a colorless solid: mp 187-188° C. (dec); NMR (CDCl₃) δ0.82 (t, J=7Hz, 3H), 1.21-1.34 (m, 2H), 1.35-1.46 (m, 2H), 1.87 (s, 6H), 2.19 (s,3H), 2.24 (t, J=8 Hz, 2H), 4.76 (s, 2H), 5.79 (s, 1H), 6.54 (s, 2H),7.08 (d, J=8 Hz, 2H), 7.17 (d, J=8 Hz, 2H), 7.44-7.63 (m, 3H), 7.77 (dd,J=8 and 2 Hz, 1H); MS (FAB) m/e (rel intensity) 493 (15), 207 (100), 178(18); HRMS. Calc'd for M+H: 493.2716. Found: 493.2694.

EXAMPLE 9

[0463]

[0464] 1- (2,6-dimethyl-4-tertbutylphenyl) -4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one

[0465] Step 1: Preparation of 1-(2,6-dimethyl-4-tertbutylphenyl)-4-butyl-1,3-dihydro-2H-imidazol-2-one.

[0466] Following General Synthetic Scheme III, 1-(2,6-dimethyl-4-tertbutylphenyl)-4-butyl-1,3-dihydro-2H-imidazol -2-one was prepared:NMR (CDCl₃) δ0.90 (t, J=8 Hz, 3H), 1.26-1.42 (m, 2H), 1.30 (s, 9H),1.48-1.60 (m, 2H), 2.18 (s, 6H), 2.40 (t, J=8 Hz, 2H), 5.83 (s, 1H),7.11 (s, 2H), 10.30 (br s, 1H).

[0467] Step 2: Preparation of 1-(2,6-dimethyl-4-tertbutylphenyl)-4-butyl-1,3-dihydro-3-[2′-1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one.

[0468] Following General Synthetic Scheme VI, the imidazol-2-one fromStep 1 was converted to 1-(2,6-dimethyl-4-tertbutylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-oneas a colorless solid: mp 134-135° C.; NMR (CDCl₃) δ0.85 (t, J=7 Hz, 3H)1.23-1.51 (m, 4H), 1.28 (s, 9H), 1.94 (s, 6H), 2.30 (t, J=8 Hz, 2H) ,4.79 (s, 2H) , 5.87 (s, 1H) , 6.98 (d, J=9 Hz, 4H), 7.07 (d, J=9 Hz,2H), 7.38-7.44 (m, 1H), 7.47-7.53 (m, 1H), 7.54-7.62 (m, 1H), 7.80 (d,J=8 Hz, 1H); MS (FAB) m/e (rel intensity) 535 (19), 207 (100), 178 (31);HRMS. Calc'd for M+H: 535.3185. Found: 535.3192.

BIOLOGICAL EVALUATION

[0469] Assay A: Angiotensin II Binding Activity

[0470] Compounds of the invention were tested for ability to bind to thesmooth muscle angiotensin II receptor using a rat uterine membranepreparation. Angiotensin II (AII) was purchased from Peninsula Labs.¹²⁵I-angiotensin II (specific activity of 2200 Ci/mmol) was purchasedfrom Du Pont-New England Nuclear. Other chemicals were obtained fromSigma Chemical Co. This assay was carried out according to the method ofDouglas et al [Endocrinology, 106, 120-124 (1980)]. Rat uterinemembranes were prepared from fresh tissue. All procedures were carriedout at 4° C. Uteri were stripped of fat and homogenized inphosphate-buffered saline at pH 7.4 containing 5 mM EDTA. The homogenatewas centrifuged at 1500 ×g for 20 min., and the supernatant wasrecentrifuged at 100,000 ×g for 60 min. The pellet was resuspended inbuffer consisting of 2 mM EDTA and 50 mM Tris-HCl (pH 7.5) to a finalprotein concentration of 4 mg/ml. Assay tubes were charged with 0.25 mlof a solution containing 5 mM MgCl_(2,) 2 mM EDTA, 0.5% bovine serumalbumin, 50 mM Tris-HCl, pH 7.5 and ¹²⁵I-AII (approximately 10⁵ cpm) inthe absence or in the presence of unlabelled ligand. The reaction wasinitiated by the addition of membrane protein and the mixture wasincubated at 25° C. for 60 min. The incubation was terminated withice-cold 50 mM Tris-HCl (pH 7.5) and the mixture was filtered toseparate membrane-bound labelled peptide from the free ligand. Theincubation tube and filter were washed with ice-cold buffer. Filterswere assayed for radioactivity in a Micromedic gamma counter.Nonspecific binding was defined as binding in the presence of 10 μM ofunlabelled AII. Specific binding was calculated as total binding minusnonspecific binding. The receptor binding affinity of an AII antagonistcompound was indicated by the concentration (IC₅₀) of the tested AIIantagonist which gives 50% displacement of the total specifically bound¹²⁵I-AII from the high affinity AII receptor. Binding data were analyzedby a nonlinear least-squares curve fitting program. Results are reportedin Table I.

[0471] Assay B: In Vitro Vascular Smooth Muscle-Response for AII

[0472] The compounds of the invention were tested for antagonistactivity in rabbit aortic rings. Male New Zealand white rabbits (2-2.5kg) were sacrificed using an overdose of pentobarbital and exsanguinatedvia the carotid arteries. The thoracic aorta was removed, cleaned ofadherent fat and connective tissue and then cut into 3-mm ring segments.The endothelium was removed from the rings by gently sliding a rolled-uppiece of filter paper into the vessel lumen. The rings were then mountedin a water-jacketed tissue bath, maintained at 37° C., between moveableand fixed ends of a stainless steel wire with the moveable end attachedto an FT03 Grass transducer coupled to a Model 7D Grass Polygraph forrecording isometric force responses. The bath was filled with 20 ml ofoxygenated (95% oxygen/5% carbon dioxide) Krebs solution of thefollowing composition (mM): 130 NaCl, 15 NaHCO_(3,) 15 KCl, 1.2NaH₂P0_(4,) 1.2 MgS0_(4,) 2.5 CaCl₂, and 11.4 glucose. The preparationswere equilibrated for one hour before approximately one gram of passivetension was placed on the rings. Angiotensin II concentration-responsecurves were then recorded (3×10⁻¹⁰ to 1×10⁻⁵ M). Each concentration ofAII was allowed to elicit its maximal contraction, and then AII waswashed out repeatedly for 30 minutes before rechallenging with a higherconcentration of AII. Aorta rings were exposed to the test antagonist at10⁻⁵ M for 5 minutes before challenging with AII. Adjacent segments ofthe same aorta ring were used for all concentration-response curves inthe presence or absence of the test antagonist. The effectiveness of thetest compound was expressed in terms of pA₂ values and were calculatedaccording to H.O. Schild [Br. J. Pharmacol. Chemother., 2,189-206(1947)]. The pA₂ value is the concentration of the antagonist whichincreases the EC₅₀ value for AII by a factor of two. Each testantagonist was evaluated in aorta rings from two rabbits. Results arereported in Table I.

[0473] Assay C: In Vivo Intragastric Pressor Assay Response for AllAntagonists

[0474] Male Sprague-Dawley rats weighing 225-300 grams were anesthetizedwith methohexital (30 mg/kg, i.p.) and catheters were implanted into thefemoral artery and vein. The catheters were tunneled subcutaneously toexit dorsally, posterior to the head and between the scapulae. Thecatheters were filled with heparin (1000 units/ml of saline). The ratswere returned to their cage and allowed regular rat chow and water adlibitum. After full recovery from surgery (3-4 days), rats were placedin Lucite holders and the arterial line was connected to a pressuretransducer. Arterial pressure was recorded on a Gould polygraph (mmHg).Angiotensin II was administered as a 30 ng/kg bolus via the venouscatheter delivered in a 50 μl volume with a 0.2 ml saline flush. Thepressor response in mm Hg was measured by the difference frompre-injection arterial pressure to the maximum pressure achieved. TheAII injection was repeated every 10 minutes until three consecutiveinjections yielded responses within 4 mmHg of each other. These threeresponses were then averaged and represented the control response toAII. The test compound was suspended in 0.5% methylcellulose in waterand was administered by gavage. The volume administered was 2 ml/kg bodyweight. The standard dose was 3 mg/kg. Angiotensin II bolus injectionswere given at 30, 45, 60, 75, 120, 150, and 180 minutes after gavage.The pressor response to AII was measured at each time point. The ratswere then returned to their cage for future testing. A minimum of 3 dayswas allowed between tests. Percent inhibition was calculated for eachtime point following gavage by the following formula: [(ControlResponse—Response at time point)/Control Response] ×100. Results areshown in Table I. TABLE I In Vitro and In Vivo Angiotensin II Activityof Compounds of the Invention Test ³Assay C Compound ¹Assay A ²Assay BDose: 3 mg/kg (i.g.) Example # IC₅₀ (nM) pA₂ Inhibition (%) Duration(min.) 1 14 NC 20%/— 2 97 NC 70%/>180 min. 3 9.8 8.53/8.61 25%/>180 min.4 13 9.06/8.85 35%/>180 min. 5 6.3 9.07/—  40%/>180 min. 6 33 8.71/8.64<20% 7 190  —/6.54 NT 8 30 8.49/8.51 50%/>180 min. 9 270 8.06/8.25 NT

[0475] Also embraced within this invention is a class of pharmaceuticalcompositions comprising one or more compounds of Formula I inassociation with one or more non-toxic, pharmaceutically acceptablecarriers and/or diluents and/or adjuvants (collectively referred toherein as “carrier” materials) and, if desired, other activeingredients. The compounds of the present invention may be administeredby any suitable route, preferably in the form of a pharmaceuticalcomposition adapted to such a route, and in a dose effective for thetreatment intended. Therapeutically effective doses of the compounds ofthe present invention required to prevent or arrest the progress of themedical condition are readily ascertained by one of ordinary skill inthe art. The compounds and composition may, for example, be administeredintravascularly, intraperitoneally, subcutaneously, intramuscularly ortopically.

[0476] For oral administration, the pharmaceutical composition may be inthe form of, for example, a tablet, capsule, suspension or liquid. Thepharmaceutical composition is preferably made in the form of a dosageunit containing a particular amount of the active ingredient. Examplesof such dosage units are tablets or capsules. These may with advantagecontain an amount of active ingredient from about 1 to 250 mg,preferably from about 25 to 150 mg. A suitable daily dose for a mammalmay vary widely depending on the condition of the patient and otherfactors. However, a dose of from about 0.1 to 3000 mg/kg body weight,particularly from about 1 to 100 mg/kg body weight, may be appropriate.

[0477] The active ingredient may also be administered by injection as acomposition wherein, for example, saline, dextrose or water may be usedas a suitable carrier. A suitable daily dose is from about 0.1 to 100mg/kg body weight injected per day in multiple doses depending on thedisease being treated. A preferred daily dose would be from about 1 to30 mg/kg body weight. Compounds indicated for prophylactic therapy willpreferably be administered in a daily dose generally in a range fromabout 0.1 mg to about 100 mg per kilogram of body weight per day. A morepreferred dosage will be a range from about 1 mg to about 100 mg perkilogram of body weight. Most preferred is a dosage in a range fromabout 1 to about 50 mg per kilogram of body weight per day. A suitabledose can be administered, in multiple sub-doses per day. These sub-dosesmay be administered in unit dosage forms. Typically, a dose or sub-dosemay contain from about 1 mg to about 100 mg of active compound per unitdosage form. A more preferred dosage will contain from about 2 mg toabout 50 mg of active compound per unit dosage form. Most preferred is adosage form containing from about 3 mg to about 25 mg of active compoundper unit dose.

[0478] The dosage regimen for treating a disease condition with thecompounds and/or compositions of this invention is selected inaccordance with a variety of factors, including the type, age, weight,sex and medical condition of the patient, the severity of the disease,the route of administration, and the particular compound employed, andthus may vary widely.

[0479] For therapeutic purposes, the compounds of this invention areordinarily combined with one or more adjuvants appropriate to theindicated route of administration. If administered per os, the compoundsmay be admixed with lactose, sucrose, starch powder, cellulose esters ofalkanoic acids, cellulose alkyl esters, talc, stearic acid, magnesiumstearate, magnesium oxide, sodium and calcium salts of phosphoric andsulfuric acids, gelatin, acacia gum, sodium alginate,polyvinylpyrrolidone, and/or polyvinyl alcohol, and then tableted orencapsulated for convenient administration. Such capsules or tablets maycontain a controlled-release formulation as may be provided in adispersion of active compound in hydroxypropylmethyl cellulose.Formulations for parenteral administration may be in the form of aqueousor non-aqueous isotonic sterile injection solutions or suspensions.These solutions and suspensions may be prepared from sterile powders orgranules having one or more of the carriers or diluents mentioned foruse in the formulations for oral administration. The compounds may bedissolved in water, polyethylene glycol, propylene glycol, ethanol, cornoil, cottonseed oil, peanut oil, sesame oil, benzyl alcohol, sodiumchloride, and/or various buffers. Other adjuvants and modes ofadministration are well and widely known in the pharmaceutical art.

[0480] Although this invention has been described with respect tospecific embodiments, the details of these embodiments are not to beconstrued as limitations.

What is claimed is:
 1. A compound of Formula I:

wherein each of R¹, R² and R³ is independently selected from hydrido,alkyl, alkoxy, cyano, halo, hydroxy, nitro, amino, alkylamino, carboxyl,alkoxycarbonyl, formyl, alkylcarbonyl and haloalkylcarbonyl; with theproviso that at least one of R¹, R² and R³ must be a substituent otherthan hydrido, and with the further proviso that when each of R¹ and R³is hydrido, then R² cannot be chloro; wherein R⁴ is selected fromhydrido, alkyl, halo, haloalkyl, formyl, carboxyl and alkoxyalkyl;wherein R⁵ is selected from alkyl, phenyl, phenylalkyl, cycloalkyl andcycloalkylalkyl; and wherein R⁶ is an acidic group selected from COOHand

or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptablesalt thereof.
 2. Compound of claim 1 wherein each of R¹, R² and R³ isindependently selected from hydrido, methyl, ethyl, n-propyl, isopropyl,tert-butyl, methoxy, ethoxy, propoxy, isopropoxy, tert-butoxy, cyano,fluoro, chloro, bromo, iodo, hydroxy, nitro, amino, N-methylamino,N,N-dimethylamino, N-ethylamino, N,N-diethylamino, carboxyl,methoxycarbonyl, ethoxycarbonyl, formyl, methylcarbonyl, ethylcarbonyland trifluoromethylcarbonyl; with the proviso that at least one of R¹,R² and R³ must be a substituent other than hydrido, and with the furtherproviso that when each of R¹ and R³ is hydrido, then R² cannot bechloro; wherein R⁴ is selected from hydrido, methyl, fluoro, chloro,monofluoromethyl, difluoromethyl, trifluoromethyl, formyl, carboxyl anddimethoxymethyl; wherein R⁵ is selected from methyl, ethyl, n-propyl,isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl,isopentyl, neopentyl, phenyl, benzyl, phenethyl, cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl,cyclopropylethyl, cyclobutylmethyl, cyclobutylethyl, cyclopentylmethyl,cyclopentylethyl, cyclohexylmethyl and cyclohexylethyl; and wherein R⁶is an acidic group selected from COOH and

or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptablesalt thereof.
 3. Compound of claim 2 wherein R¹ is selected from methyl,ethyl, n-propyl, isopropyl, tert-butyl, hydroxy, methoxy, fluoro, bromo,iodo, carboxyl, amino, cyano, formyl, methylcarbonyl andtrifluoromethyl-carbonyl; wherein each of R², R³ and R⁴ is hydrido;wherein R⁵ is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl,sec-butyl, isobutyl, tert-butyl and n-pentyl; and wherein R⁶ is

or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptablesalt thereof.
 4. Compound of claim 3 selected from compounds, theirstereoisomers and tautomers, and the pharmaceutically-acceptable saltsthereof, said compounds consisting of1-(2-methylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-ethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-propylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-isopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-tertbutylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-fluorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-chlorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol -5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-bromophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-iodophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-methoxyphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-hydroxyphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-cyanophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-carboxyphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-aminophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-acetylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one; and1-(2-trifluoroacetylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one. 5.Compound of claim 2 wherein each of R¹, R² and R³ is independentlyselected from methyl, ethyl, n-propyl, isopropyl, tert-butyl, hydroxy,methoxy, fluoro, bromo, iodo, carboxyl, amino, cyano, formyl,methylcarbonyl and trifluoromethyl-carbonyl; wherein R³ may further behydrido; wherein R⁴ is hydrido; wherein R⁵ is selected from methyl,ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl andn-pentyl; and wherein R⁶ is

or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptablesalt thereof.
 6. Compound of claim 5 selected from compounds, theirstereoisomers and tautomers, and the pharmaceutically-acceptable saltsthereof, said compounds consisting of1-(2,6-dimethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-ethyl-6-methylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-propyl-6-methylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-isopropyl-6-methylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-tertbutyl-6-methylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-fluoro-6-methylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-chloro-6-methylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyll-4-ylmethyl]-2H-imidazol-2-one;1-(2-bromo-6-methylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-methoxy-6-methylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-carboxy-6-methylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-acetyl-6-methylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-methyl-6-ethylphenyl)-d-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2,6-diethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-propyl-6-ethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-isopropyl-6-ethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-tertbutyl-6-ethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-fluoro-6-ethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-chloro-6-ethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-bromo-6-ethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyll-4-ylmethyl]-2H-imidazol-2-one;1-(2-methoxy-6-ethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-carboxy-6-ethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-acetyl-6-ethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-methyl-6-isopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-ethyl-6-isopropylphenyl)-4-butyl-1,3-dihydro-3- [2′-(1H-tetrazol-5-yl)[1,1′-biphenyll-4-ylmethyl]-2H-imidazol-2-one;1-(2-propyl-6-isopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2,6-diisopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-tertbutyl-6-isopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-fluoro-6-isopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-chloro-6-isopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-bromo-6-isopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H -tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-methoxy-6-isopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-carboxy-6-isopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-acetyl-6-isopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-methyl-6-tertbutylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-ethyl-6-tertbutylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-propyl-6-tertbutylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-isopropyl-6-tertbutylphenyl)-4-butyl-1,3-dihydro-3-2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2,6-ditertbutylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-fluoro-6-tertbutylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-chloro-6-tertbutylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-bromo-6-tertbutylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-methoxy-6-tertbutylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-carboxy-6-tertbutylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-acetyl-6-tertbutylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-methyl-6-fluorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-ethyl-6-fluorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-propyl-6-fluorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-isopropyl-6-fluorophenyl)-4-butyl-1,3-dihydro-3-2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-tertbutyl-6-fluorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-fluoro-6-fluorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-chloro-6-fluorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-bromo-6-fluorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-methoxy-6-fluorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-carboxy-6-fluorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-acetyl-6-fluorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-methyl-6-chlorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-ethyl-6-chlorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-propyl-6-chlorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(²-isopropyl-6-chlorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-tertbutyl-6-chlorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-fluoro-6-chlorophenyl)-4-butyl-1,3-dihydro-3-[2′-5 (1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2,6-dichlorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-bromo-6-chlorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-methoxy-6-chlorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-carboxy-6-chlorophenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl) [1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-acetyl-6-chlorophenyl)-4-butyl-1,3-dihydro-3-[′2-(1H-tetrazol -5yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol- 2-one;1-(2-methyl-6-methoxyphenyl) -4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-ethyl-6-methoxyphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-propyl-6-methoxyphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-isopropyl-6-methoxyphenyl)-4-butyl-1,3-dihydro-3-[2′(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]3-2H-imidazol--2-one;1-(2-tertbutyl-6-methoxyphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-fluoro-6-methoxyphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-chloro-6-methoxyphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-bromo-6-methoxyphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2,6-dimethoxyphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one; 1-(2-carboxy-6-methoxyphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one; and1-(2-acetyl-6-methoxyphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one.
 7. Compound ofclaim 4 which is 1-(2-ethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one or apharmaceutically-acceptable salt thereof.
 8. Compound of claim 4 whichis 1-(2-isopropylphenyl) -4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one or apharmaceutically-acceptable salt thereof.
 9. Compound of claim 6 whichis 1-(2,6-dimethoxyphenyl) -4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one or apharmaceutically-acceptable salt thereof.
 10. Compound of claim 6 whichis 1-(2-chloro-6-methylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one or apharmaceutically-acceptable salt thereof.
 11. Compound of claim 6 whichis 1-(2,6-dimethylphenyl) -4-butyl-1,3-dihydro-3-[2′1-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one or apharmaceutically-acceptable salt thereof.
 12. Compound of claim 6 whichis 1-(2,6-diethylphenyl) -4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one or apharmaceutically-acceptable salt thereof.
 13. Compound of claim 6 whichis 1-(2,6-diisopropylphenyl) -4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one or apharmaceutically-acceptable salt thereof.
 14. Compound of claim 6 whichis 1-(2,4,6-trimethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one or apharmaceutically-acceptable salt thereof.
 15. Compound of claim 6 whichis 1-(2,6-dimethyl -4-tertbutylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol -2-one or apharmaceutically-acceptable salt thereof.
 16. A pharmaceuticalcomposition comprising a therapeutically-effective amount of anangiotensin II antagonist compound and a pharmaceutically-acceptablecarrier or diluent, said antagonist compound selected from a family ofcompounds of Formula I:

wherein each of R¹, R² and R³ is independently selected from hydrido,alkyl, alkoxy, cyano, halo, hydroxy, nitro, amino, alkylamino, carboxyl,alkoxycarbonyl, formyl, alkylcarbonyl and haloalkylcarbonyl; with theproviso that at least one of R¹, R² and R³ must be a substituent otherthan hydrido, and with the further proviso that when each of R¹ and R³is hydrido, then R² cannot be chloro; wherein R⁴ is selected fromhydrido, alkyl, halo, haloalkyl, formyl, carboxyl and alkoxyalkyl;wherein R⁵ is selected from alkyl, phenyl, phenylalkyl, cycloalkyl andcycloalkylalkyl; and wherein R⁶ is an acidic group selected from COOHand

or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptablesalt thereof.
 17. The composition of claim 16 wherein each of R¹, R² andR³ is independently selected from hydrido, methyl, ethyl, n-propyl,isopropyl, tert-butyl, methoxy, ethoxy, propoxy, isopropoxy,tert-butoxy, cyano, fluoro, chloro, bromo, iodo, hydroxy, nitro, amino,N-methylamino, N,N-dimethylamino, N-ethylamino, N,N-diethylamino,carboxyl, methoxycarbonyl, ethoxycarbonyl, formyl, methylcarbonyl,ethylcarbonyl and trifluoromethylcarbonyl; with the proviso that atleast one of R¹, R² and R³ must be a substituent other than hydrido, andwith the further proviso that when each of R¹ and R³ is hydrido, then R²cannot be chloro; wherein R⁴ is selected from hydrido, methyl, fluoro,chloro, monofluoromethyl, difluoromethyl, trifluoromethyl, formyl,carboxyl and dimethoxymethyl; wherein R⁵ is selected from methyl, ethyl,n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl,isopentyl, neopentyl, phenyl, benzyl, phenethyl, cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl,cyclopropylethyl, cyclobutylmethyl, cyclobutylethyl, cyclopentylmethyl,cyclopentylethyl, cyclohexylmethyl and cyclohexylethyl; and wherein R⁶is an acidic group selected from COOH and

or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptablesalt thereof.
 18. A composition of claim 17 wherein each of R¹, R² andR³ is independently selected from methyl, ethyl, n-propyl, isopropyl,tert-butyl, hydroxy, methoxy, fluoro, chloro, bromo, iodo, carboxyl,amino, cyano, formyl, methylcarbonyl and trifluoromethylcarbonyl; withthe proviso that at least one of R¹, R² and R³ must be a substituentother than hydrido, and with the further proviso that when each of R¹and R³ is hydrido, then R² cannot be chloro; wherein R⁴ is hydrido;wherein R⁵ is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl,sec-butyl, isobutyl, tert-butyl and n-pentyl; and wherein R⁶ is

or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptablesalt thereof.
 19. The composition of claim 18 wherein said antagonistcompound is selected from compounds, their stereoisomers and tautomers,and the pharmaceutically-acceptable salts thereof, said compoundsconsisting of 1-(2-ethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-isopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2,6-dimethoxyphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-chloro-6-methylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2,6-dimethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2,6-diethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2,6-diisopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2,4,6-trimethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one; and1-(2,6-dimethyl-4-tertbutylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one.20. A therapeutic method for treating a circulatory disorder or acirculatory-related disorder, said method comprising administering to asubject susceptible to or afflicted with such disorder atherapeutically-effective amount of an active compound of Formula I:

wherein each of R¹, R² and R³ is independently selected from hydrido,alkyl, alkoxy, cyano, halo, hydroxy, nitro, amino, alkylamino, carboxyl,alkoxycarbonyl, formyl, alkylcarbonyl and haloalkylcarbonyl; with theproviso that at least one of R¹, R² and R³ must be a substituent otherthan hydrido, and with the further proviso that when each of R¹ and R³is hydrido, then R² cannot be chloro; wherein R⁴ is selected fromhydrido, alkyl, halo, haloalkyl, formyl, carboxyl and alkoxyalkyl;wherein R⁵ is selected from alkyl, phenyl, phenylalkyl, cycloalkyl andcycloalkylalkyl; and wherein R⁶ is an acidic group selected from COOHand

or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptablesalt thereof.
 21. The method of claim 20 wherein each of R¹, R² and R³is independently selected from hydrido, methyl, ethyl, n-propyl,isopropyl, tert-butyl, methoxy, ethoxy, propoxy, isopropoxy,tert-butoxy, cyano, fluoro, chloro, bromo, iodo, hydroxy, nitro, amino,N-methylamino, N,N-dimethylamino, N-ethylamino, N,N-diethylamino,carboxyl, methoxycarbonyl, ethoxycarbonyl, formyl, methylcarbonyl,ethylcarbonyl and trifluoromethylcarbonyl; with the proviso that atleast one of R¹, R² and R³ must be a substituent other than hydrido, andwith the further proviso that when each of R¹ and R³ is hydrido, then R²cannot be chloro; wherein R⁴ is selected from hydrido, methyl, fluoro,chloro, monofluoromethyl, difluoromethyl, trifluoromethyl, formyl,carboxyl and dimethoxymethyl; wherein R⁵ is selected from methyl, ethyl,n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl,isopentyl, neopentyl, phenyl, benzyl, phenethyl, cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl,cyclopropylethyl, cyclobutylmethyl, cyclobutylethyl, cyclopentylmethyl,cyclopentylethyl, cyclohexylmethyl and cyclohexylethyl; and wherein R6is an acidic group selected from COOH and

or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptablesalt thereof.
 22. The method of claim 21 wherein each of R¹, R² and R³is independently selected from methyl, ethyl, n-propyl, isopropyl,tert-butyl, hydroxy, methoxy, fluoro, chloro, bromo, iodo, carboxyl,amino, cyano, formyl, methylcarbonyl and trifluoromethylcarbonyl; withthe proviso that at least one of R¹, R² and R³ must be a substituentother than hydrido, and with the further proviso that when each of R¹and R³ is hydrido, then R² cannot be chloro; wherein R⁴ is hydrido;wherein R⁵ is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl,sec-butyl, isobutyl, tert-butyl and n-pentyl; and wherein R⁶ is

or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptablesalt thereof.
 23. The method of claim 22 wherein said compound isselected from compounds, their stereoisomers and tautomers, and thepharmaceutically-acceptable salts thereof, said compounds consisting of1-(2-ethylphenyl)-4-butyl-1,3-dihydro-3-[2′1-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-isopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2,6-dimethoxyphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2-chloro-6-methylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2,6-dimethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2,6-diethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2,6-diisopropylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one;1-(2,4,6-trimethylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one; and1-(2,6-dimethyl-4-tertbutylphenyl)-4-butyl-1,3-dihydro-3-[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-ylmethyl]-2H-imidazol-2-one.
 24. Themethod of claim 20 wherein said circulatory disorder is a cardiovasculardisorder.
 25. The method of claim 24 wherein said cardiovasculardisorder is hypertension.
 26. The method of claim 24 wherein saidcardiovascular disorder is congestive heart failure.
 27. The method ofclaim 20 wherein said circulatory-related disorder is glaucoma.